Cyclin E and Cks proteins are frequently overexpressed in a broad spectrum of human cancers, and as we have shown for breast cancer, often in the same tumors. Yet, how these proteins contribute to oncogenesis is poorly understood. Compounding the problem of understanding their roles in oncogenesis is an incomplete delineation of their basic biological functions. In this proposal we aim to address both of these issues. We will use a combination of biochemical, cell based and animal based approaches in the hope of providing a comprehensive picture of how these proteins function individually and in concert during the cell cycle and in oncogenesis.